Our main objective is the immunotherapy of mouse leukemias by use of potent, specific antisera, coupled with chemotherapy and immune stimulation. These model system studies are intended to be of use in clinical treatment of leukemia. Our approach to the immunotherapy of mouse leukemias is to use rabbit antisera of 'directed' specificity (Reif et al., Ann. N. Y. Acad. Sci. 277: 647-669, 1976). Because these antisera are not sufficiently potent to perform cures in meaningful mouse test systems, we have used chemotherapy with cyclophosphamide to reduce tumor mass. Under these conditions, we can get 'cures', but only if the antigenicity of the tumor cells (or so it seems) is sufficiently high. We are presently exploring the question of whether tumor cell antigenicity is indeed the crux of success for immunotherapy. We have (with Dr. P. L. Southwick and K. P. Judd) described a new compound for skin sensitization, NOPYE (Fed. Proc. 36: 1060, 1977). We plan to test more newly synthesized compounds for skin sensitization in order to look for compounds that might be more effective than DNCB in immunotherapy of skin tumors. We also plan to test such compounds, after coupling to tumor cells, for any increase in immunogenicity using three newly-derived tumors of C57BL/6, which have just been developed in our laboratory. Finally, we are attempting to develop a new test for microcytotoxicity testing that will be more automatic in evaluation than past tests. We need such a test to understand more fully the role of host cells and serum factors during the various phases of tumor invasion and rejection following injection of tumor, and its treatment with immunotherapy and chemotherapy.